Under- and overdosing of DOACs still common in patients with AF

Determinants for under- and overdosing of direct oral anticoagulants and physicians' implementation of clinical pharmacists' recommendations

Literature - Moudallel S, Cornu P, Dupont A et al. - Br J Clin Pharmacol. 2021 Jul 31. doi: 10.1111/bcp.15017.

Introduction and methods

Several studies have shown that inappropriate DOAC prescribing is a common problem [1-19]. This study identified DOAC specific determinants of under- and overdosing in hospitalized patients with AF.

The cross-sectional single center study was conducted at the UZ Brussel in Belgium. All hospitalized patients with AF who were initiated on or continued with dabigatran, apixaban, edoxaban or rivaroxaban between 1 January 2019 and 31 December 2019 were included (n=1688). The primary outcome was the proportion of patients with an inappropriate DOAC prescription (i.e. a deviation from the recommended dose in the Summary of Product Characteristics [SmPC]) and the identification of determinants related with DOAC under- and overdosing. Secondary outcomes included acceptance and implementation rates of pharmacists’ dosing advices.

Main results

  • A total of 286 patients (16.9%) received an inappropriate DOAC prescription. Underdosing was seen in 9.7%, overdosing in 6.9% and contraindications in 0.4% of patients.
  • Taken all four DOACs together, determinants associated with a significantly lower odds of underdosing were body weight <60 kg (adjusted (a) OR 0.46, 95%CI 0.27-0.77), use of edoxaban compared to rivaroxaban (aOR 0.42, 95%CI 0.24-0.74), undergoing surgery (aOR 0.57, 95%CI 0.37-0.87), and being DOAC naive (aOR 0.45, 95%CI 0.29-0.71). Having a bleeding history (aOR 1.86, 95%CI 1.24-2.80) and the use of narcotic analgesics (aOR 1.67, 95%CI 1.13-2.46) were associated with a significantly higher odds of underdosing.
  • Use of dabigatran (aOR 0.24, 95%CI 0.08-0.71) and apixaban (aOR 0.18, 95%CI 0.10-0.32) compared to use of rivaroxaban were associated with a lower odds of overdosing. Determinants associated with a significantly higher odds of overdosing were renal impairment (aOR 11.29, 95% CI 6.23-20.45) and body weight <60 kg (aOR 2.34, 95%CI 1.42-3.85).
  • For rivaroxaban users, a decreased renal function was associated with higher odds of overdosing compared to patients with normal renal function (aOR 100.95, 95% 23.23-438.70). In patients with CrCl <50 mL/min, a lower odds of underdosing was observed (aOR 0.17, 95%CI 0.06-0.48).
  • Determinants associated with a significantly higher odds of overdosing in patients using edoxaban were decreased renal function (aOR 3.25, 95%CI 1.49-7.12) and body weight <60 kg (aOR 4.16, 95%CI 1.97-8.77).
  • For apixaban users, body weight <60 kg (aOR 0.26, 95%CI 0.12-0.55) was a risk factor for underdosing and having a history of bleeding was associated with a higher odds of underdosing (aOR 2.14, 95%CI 1.22-3.75).
  • In 79.2% of cases, physicians accepted the dosing advices by clinical pharmacists and in 65.5% of cases the advice was effectively implemented by the physicians.


This cross-sectional single center study found inappropriate DOAC prescriptions in 16.9% of hospitalized patients with AF. Underdosing was more prevalent than overdosing. Moreover, this study identified DOAC specific determinants of under- and overdosing.


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Find this article online at Br J Clin Pharmacol.

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